Colo-rectal carcinoma is one of the most common tumors in industrialized world; with an incidence of approximately 421,000 new cases/year world-wide, it is second only to lung and mammary tumors in causing death. The rate of patients curable with surgery only is approximately 45-50%. The others may be treated with combination chemotherapy which allows to a complete remission rate of no more than 5%.
Colo-rectal tumors are usually refractory or poorly sensitive to available chemotherapy and the only agent which provides some responses against this cancer is 5-Fluorouracil.
So far no therapeutic alternatives exist after the failure of the first-line combination chemotherapy essentially based on 5-FU.
Despite many new investigational agents are undergoing preclinical and clinical studies against colorectal cancer, it is generally believed that only compounds with innovative structures and possible new mechanisms of action may be successful against this highly refractory tumor hystotype.
Therefore the search for new active drugs in this indication still represents one of the most interesting and attractive field in oncology.
We have now discovered a new class of compounds, namely 4-ureido and thioureido 2(5H)-furanones, respectively 2(5H)-thiophenones, which possesses a marked antitumor activity, especially against colon cancers.
Phenylureido furanones have been already described having activity as defoliants (Reissue U.S. Patent 27,894), as herbicides (JP 63-174983) or in Bull.Chem.Soc.Jpn. Vol. 60, 2139ff as intermediates. However, no pharmaceutical activity, especially antitumour activity, has been reported in these documents. Only DE-A-25 16 555 describes 1-tert.alkyl-3-(substituted furyl)-urea-derivatives with an antihypertensive activity.